LL-37 is a recently described human antibacterial peptide that is constitutively present in human granulocytes and testis and is inducibly synthesized by human keratinocytes. This cationic, 37-amino acid peptide assumes an amphipathic a-helical conformation and is structurally distinct from all other antibacterial peptides heretofore identified in nature. The expression of the gene encoding LL-37 is induced in a number of skin inflammatory disorders and the peptide has been immunochemically localized throughout the epidermis in regions of inflamed but not normal skin(2). Hence, its presence in the epidermis of patients with skin disorders could represent an antimicrobial obstacle that bacterial pathogens would need to overcome to establish an infection. Very limited information is currently available regarding the antibacterial action of LL-37. It is the purpose of this pilot project to ascertain how its structure relates to its antimicrobial function. We will use synthetic peptide chemistry procedures to identify the amino acids of LL-37 needed for its broad-spectrum antibacterial action against two diverse bacterial that cause significant, serious skin infections.